tbuckley/cabot-search huggingface dataset:
IMMU-05. Integrative transcriptomic analysis of pilocytic astrocytomas reveals CNS region-associated characteristics
Authors: Jacob S Rozowsky, Mariëtte E G Kranendonk, Antoinette Y N Schouten- van Meeteren, Lisethe Meijer, Eelco W Hoving, Friso G Calkoen, Pieter Wesseling, Lennart A Kester, Jasper van der Lugt
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Recent insights highlight how the initiation and growth of gliomas is governed by interactions between glioma stem-like cells and stromal and immune cells in the tumor microenvironment. For pilocytic astrocytomas, the most common pediatric CNS tumor, this relationship is so far less explored. To this end, we used transcriptomic methods to investigate inter-patient heterogeneity, and the stromal and immune microenvironment of pilocytic astrocytomas. MATERIALS AND METHODS: In this study, we collected clinical data and tissue of 90 pre-treatment pilocytic astrocytomas from different CNS compartments: posterior fossa (n=57), supratentorial (n=23), and spinal (n=10). The median age at primary resection was 8 (0-16) years, and 66% (n=59) of our cohort was male. From 10 of these patients, we collected post-treatment samples after re-growth of the tumor as well. We characterized all samples by bulk RNA-sequencing and DNA methylation profiling, and selected a subset (n=10) samples for single-nucleus RNA-sequencing. RESULTS: Principal component analysis and unsupervised clustering of bulk sequencing data revealed gene expression patterns correlating to the CNS location of the tumor, consistent with prior reports. Using differential expression and functional pathway analysis, we found CNS region-associated enrichment of cell-cycle, developmental, and inflammatory-related pathways. With respect to the glioma immune microenvironment, supratentorial tumors were enriched in gene-sets related to T-cell activation and cytotoxicity, while spinal tumors had lowest expression of immune-related genes. Moreover, spinal tumors were enriched in pathways related to cell division, nucleotide synthesis, and neurodevelopment. To resolve cell-type expression programs of glioma and immune cells in the microenvironment, we collected and analyzed snRNA-seq data of 10 pilocytic astrocytomas, as well as harmonized our findings with a pre-existing dataset from Vladoiu, 2019. CONCLUSION: Our integrative transcriptomic analysis of pilocytic astrocytomas highlights CNS region-associated differences in expression programs of the glioma cells and in the immune cell composition of the tumor microenvironment.
Real-world evidence of impact of atrial fibrillation (AF) on clinical and economic outcomes in patients with chronic lymphocytic leukemia (CLL).
Authors: Keri Yang, Tom Liu, Boxiong Tang, Asher Chanan-Khan
Journal: Journal of Clinical Oncology (2022)

e18729 Background: While the incidence of AF in CLL has been increasing, the implications of AF in real-world CLL patients remain understudied. This study aimed to assess the impact of AF on clinical and economic outcomes in CLL patients. Methods: This retrospective observational study used the US IBM MarketScan ® commercial claims/Medicare supplement database (2017-2020) to identify newly diagnosed CLL patients (≥18 years) and incidence of AF after index date, defined as the first CLL diagnosis date. Patients were followed for ≥3-months pre-index, and from index to last follow-up or death. In addition to patient characteristics, clinical outcomes (incidence of heart failure [HF], bleeding and stroke) and economic outcomes (costs and healthcare resource utilization [HRU]) were compared between CLL patients with AF (CLL+AF) and CLL patients without AF (CLL-AF). HRU was evaluated by inpatient, outpatient, ER, and pharmacy visits. Multivariable regression analyses were conducted to examine the association between AF and clinical outcomes. Results: Among a total of 16,800 newly diagnosed CLL patients included in the study, 20% developed AF. CLL+AF were significantly older than CLL-AF (median: 77 vs 62 years; P &lt; .001). Compared to CLL-AF, CLL+AF also had significantly more comorbidities at baseline, as shown by higher Charlson comorbidity index (CCI) (median: 1.0 vs 3.0; P &lt; .001) and more patients with previous AF history (0.3% vs 8.4%; P &lt; .001). Further assessing clinical outcomes in CLL+AF vs CLL-AF, significantly higher incidence of HF (26.3% vs 3.0%; P &lt; .001), bleeding (12.2% vs 4.8%; P &lt; .001) and stroke (6.6% vs 1.2%; P &lt; .001) were observed. For HRU, CLL+AF were reported to have significantly higher rates of ER visits (29.4% vs 12.9%; P &lt; .001) and hospitalizations (42.2% vs 14.5%; P &lt; .001) than CLL-AF. In CLL+AF, the average total AF-related costs were $13,520.21 within 30 days after AF diagnosis, and $22,304.82 within 60 days after AF diagnosis. Controlling for demographics and comorbidities, multivariable regressions reported statistically significant associations between AF and HF, as well as AF and stroke (Table). Conclusions: This real-world study reported significantly higher incidence of HF, bleeding and stroke incurred by CLL patients who developed AF compared with those who did not. The presence of HF, bleeding and stroke further increased HRU and costs. These findings highlight the importance of better disease management and treatment selection to prevent AF in CLL patients.[Table: see text]
Short-term Health Insurance Plans Come Up Short for Patients With Cancer
Authors: Justin M. Barnes, Fumiko Chino
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Short-term preoperative endocrine therapy allows to estimate and revert patient prognosis with further treatment plan correction in HR+ HER2- early breast cancer patients.
Authors: Lyudmila Zhukova, Inna Ganshina, Maria Ignatieva, Maria Ivanyuk, Irina Vladimirovna Kolyadina, Gurami Kvetenadze, Alexandra Valeeva, Irina Sorokina
Journal: Journal of Clinical Oncology (2022)

e12628 Background: The anomaly function of ER/PR-dependent molecular cascade is a key driver of ER-positive HER2-negative breast cancer (HR+ HER2- BC) progression. Ki67&gt;10% and/or grade 3 (G3) determine the initial poor patient (pts) prognosis in this group. The short-term pre-operative endocrine therapy (P-ET) simply allows to look ahead to properly the further adjuvant therapy (AT) and to estimate the endocrine therapy (ET) sensibility of each pts in the routine clinical practice. The existing diagnostic methods weaknesses for the baseline lymph nodes invasion, high BC heterogeneity do not allow to accurately estimate the disease stage and tumor phenotype, respectively, with 100% accuracy before surgery. In addition to pre-ET the post-operative IHC is a base method for further pts treatment plan especially for high heterogenicity breast tumors. Our study is focused on pts proportion estimation with P-ET benefit or tumor phenotype reversion in patients with early HR+ HER2- BC. Methods: HR+ HER2- BC pts stages I-II any level of Ki67 independent from grade have received P-ET (letrozole (L)/anastrozole (A)/tamoxifen (TAM)) no less than 2 weeks until surgery in MCSC named after A.S. Loginov. Enrollment period runs from Jun’21 and will end with 1,000 pts. The primary goal of the study was pts’s proportion evaluation with baseline Ki67&gt;10% who experienced suppression of the proliferation marker to 10% or less and/or phenotype change during P-ET followed by AT strategy amendment. Results: At the data cut-off (Jan’22) 832 pts (5 pts were men) with HR+ HER2- BC were enrolled (IIT population) with median age 61 (range:26-85) and ECOG 0-2. 736 (89%) pts have baseline Ki67&gt;10% of whom 100 (14%) pts - with G3, 291 (35%) pts - with baseline Ki67≥30%. Tumors of the 398 (54%) pts suppressed proliferation marker Ki67≤ 10% and 352 (88%) pts among them avoid planned adjuvant chemotherapy followed by ET prolongation independent of ET type (L/A/TAM). The median time of P-ET amounted to 39,5 days (range: 14-90) in focused group. Post-operative evaluation of specimens in 20 (2,4%) pts have resulted in the identification of phenotype change to HER2+ BC and TNBC with subsequent modification of AT decisions (including anti-HER2-based and/or dose dense regimens). Conclusions: In HR+ HER2- early BC pts short-term P-ET simply allows to estimate pts prognosis and further AT strategy proper planning: to identify the pts population of whom CT can be avoided while maintaining treatment efficacy with a better quality of life (42% pts of IIT) (1), to radically change the planned AT to achieve optimal treatment results (2,4% pts of IIT) (2).
The long-term analysis of prognostic role of mutational status in primary resectable gastrointestinal stromal tumors (GIST).
Authors: Pawel Sobczuk, Elzbieta Bylina, Anna Klimczak, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2022)

e23517 Background: Radical surgery is the primary treatment for GIST, but up to 50% of patients relapse, mainly in form of hepatic and peritoneal metastases. GISTs are a group of tumors with various pathological and molecular features as well as different clinical courses. The aim of the study was the long-term analysis of prognostic role of mutational status in primary GIST after radical resection. Methods: The material consisted of a group of 304 patients with primary GIST diagnosed till 04/2012, with known mutational status and treated surgically with curative intend without adjuvant imatinib. Data were collected prospectively as part of the GIST clinical register. Relapse-free survival (RFS) was calculated from the date of GIST resection to the date of local recurrence, distant metastatic disease or last follow-up. Overall survival (OS) was calculated from the date of resection to the date of last follow-up or death. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate Cox regression was performed to asses impact of mutational status on RFS and OS. Results: The primary tumor (PT) locations were: gastric (57.6%) vs non-gastric (42.4%). The median of tumor size was 7cm (0.5-33 cm). Mitotic index was ≤5 in 54.3%, &gt; 5 in 45.7%. Mutations in KIT gene exon 11 were as follow: del 557-558 in 22.7% or other (point mutations, other deletions or insertions) in 40.1% with similar rates in gastric and non-gastric GIST. KIT gene exon 9 dup 502-503 (7.2%) were more common in non-gastric vs gastric GIST (16.3% vs 0.6%). PDGFR D842V was observed in 26 patients (8.6%) while other mutations in PDGFRA gene in 17 (5.6%). The median follow-up was 25.1 months. Disease recurrence was observed in 124 cases (40.8%) resulting in median RFS of 84.4 (95%CI 48.3-120.5) months. The negative independent risk factors for RFS in univariate analysis were: primary tumor location, tumor size, mitotic index and KIT exon 9 dup 502-503 mutation (P &lt; 0.05). In the multivariate analysis independent predictive factors for RFS were mitotic index &gt; 5 (HR 4.38, 95%CI 2.82-6.78), PT location (HR 1.56, 95%CI 1.01-2.39). In multivariate analysis in patients with gastric GIST PDGFR D842V mutations were significantly correlated with better RFS (HR 0.16, 95%CI 0.04-0.61), what was not observed in non-gastric GIST. The median OS was 198.1 months. The negative independent risk factors for OS in univariate analysis were: primary tumor location, primary tumor size and KIT gene exon 9 dup 502-503 mutation. Mitotic index was also negative independent risk factors in a multivariate analysis (HR 1.70, 95%CI 1.15 -2.52). Conclusions: In the long-term analysis mutational status of primary resectable GIST is related to risk of relapse especially in gastric location, however it has no independent impact on overall survival. Genotype should be included in modern risk classification of GIST.
Opioid Use Disorder, Sleep Deficiency, and Ventilatory Control: Bidirectional Mechanisms and Therapeutic Targets
Authors: Danny J. Eckert, H. Klar Yaggi
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Opioid use continues to rise globally. So too do the associated adverse consequences. Opioid use disorder (OUD) is a chronic and relapsing brain disease characterized by loss of control over opioid use and impairments in cognitive function, mood, pain perception, and autonomic activity. Sleep deficiency, a term that encompasses insufficient or disrupted sleep due to multiple potential causes, including sleep disorders, circadian disruption, and poor sleep quality or structure due to other medical conditions and pain, is present in 75% of patients with OUD. Sleep deficiency accompanies OUD across the spectrum of this addiction. The focus of this concise clinical review is to highlight the bidirectional mechanisms between OUD and sleep deficiency and the potential to target sleep deficiency with therapeutic interventions to promote long-term, healthy recovery among patients in OUD treatment. In addition, current knowledge on the effects of opioids on sleep quality, sleep architecture, sleep-disordered breathing, sleep apnea endotypes, ventilatory control, and implications for therapy and clinical practice are highlighted. Finally, an actionable research agenda is provided to evaluate the basic mechanisms of the relationship between sleep deficiency and OUD and the potential for behavioral, pharmacologic, and positive airway pressure treatments targeting sleep deficiency to improve OUD treatment outcomes.
Cell-free RNA in liquid biopsy and biomarkers profiling of hematologic and solid tumors.
Authors: Maher Albitar, Hong Zhang, Ahmad Charifa, Andrew Ip, Ivan De Dios, Wanlong Ma, James McCloskey, Michele Donato, David Samuel DiCapua Siegel, Stanley E. Waintraub, Martin Gutierrez, Andrew L Pecora, Andre Goy
Journal: Journal of Clinical Oncology (2022)

3047 Background: Expressed RNA can capture mutations, changes in expression levels due to methylation, and provide information on cell of origin, growth, and proliferation status. We developed an approach to isolate fragmented RNA from peripheral blood plasma and explored its potential to be used in liquid biopsy. Methods: Peripheral blood cfRNA was extracted from patients with neoplasms in B-cell (#105), T-cell (#16), Myeloid (#73), and from solid tumors (#44), Normal individuals (#51), and reactive post-transplant (#137). RNA was sequenced using a 1459-gene panel. Expression profile was generated using Cufflinks. Results: cfRNA levels of various solid tumor biomarkers (CA-125, CA-15-3, CEA 8, Keratin19, Keratin6A...) were significantly higher (P &lt; 0.0001) in samples from solid tumors as compared with normal control. Similarly, cfRNA lymphoid markers (CD19, CD22, CD79A, and CD79B...) and cfRNA myeloid markers (CD33, CD14, CD117, CD56...) were all higher in B-cell lymphoid neoplasms and myeloid neoplasms, respectively (P &lt; 0.0001), as compared with control. In evaluating the host immune system, cfRNA CD4:CD8B and CD3D:CD19 ratios in normal controls were as expected (median: 5.92 and 6.87, respectively) and were significantly lower in solid tumors (median 3.40 and 2.23, respectively, P &lt; 0.0002). Solid tumor cfRNA showed CTLA4:CD8B ratio significantly higher in tumors than in normal (median 0.74 vs 0.19, P = 0.0001), while there was no difference in cfRNA PD-L1:CD8B ratio (median 1.45 vs 1.77, P = 0.96). Similar distinct patterns are noted for various cytokine and chemokines. cfRNA was highly predictive of diagnosis (AUC &gt; 0.98) of solid tumors, B-cell lymphoid neoplasms, T-cell lymphoid neoplasms, and myeloid neoplasms as compared with normal control. When a specific neoplastic disease was considered against all cases including control and other neoplasms, the AUC varied between 0.77 and 0.949. Conclusions: This data shows that liquid biopsy using targeted sequencing of cfRNA in patients with various types of cancer provides comprehensive and reliable information on the neoplastic disease as well as the host. [Table: see text]
Diagnostic efficacy of deep learning-based prediction of origin for patients with cancers of unknown primary.
Authors: Lan Lan, Bin Wang, Haiyan Sun, Dong You, Yuman Zhang, Xing Li, Kai Wang
Journal: Journal of Clinical Oncology (2022)

e13560 Background: Despite of routine medical history inquiry, laboratory analysis, histopathological analyses, endoscopy and imaging methods, 3-5% of metastatic cancers are diagnosed with unknown primary (CUP). It poses a considerable challenge as modern therapeutic options for patients with CUP are mainly limited to empirical chemotherapy (paclitaxel, carboplatin, etc.), leading to an overall poor prognosis. In current clinical trials (CUPISCO trial, PACET-CUP trial) targeting CUP for precision therapy, genomic data suggest that only 31% of CUP patients could be matched for at least one targeted or immune agent. The determination of primary tumor origin and genetic mutations could probably provide more therapeutic choices and help to significantly improve the outcome in CUP patients. Methods: To identify the primary lesion of CUP, we built a weighted ensemble model by Automated machine learning, including 13 models ( XGBoost, RandomForestGini, ExtraTreesGini, etc.), using genetic and clinical datasets containing 22,018 patients of 28 tumor types, enrolled between 2016-2021. Our genetic and clinical datasets contained 10 features including age, tumor site, gene alteration, TMB, etc. Among them, 813 sites related to tumor were covered by gene alteration. The 5-fold Cross-Validation method was used to estimate the accuracy of our diagnosis models. Results: The models were evaluated using top-k differential diagnosis accuracy, which measured how frequently the top-k predictions capture any of the primary diagnoses in the reference standard. Our diagnostic model was then performed on 8 CUP patients. All of them were successfully confirmed their diagnosis of primary origin tumor. Among these patients, 2/8 CUP patients have begun relevant systemic therapy based on the confirmed diagnosis: 1 patient with diagnosis of esophageal squamous cell carcinoma receiving the immune combination TP Regimen (Albumin paclitaxel plus cisplatin) and achieved a 9-month PFS; another patient diagnosed as colorectal cancer achieved a 2-month PFS after treatment with Oxaliplatin-based chemotherapy regimen. Preliminary results of our study demonstrated the efficiency of this Artificial Intelligence model for the diagnosis in CUP patients. Conclusions: We developed a diagnostic model on CUP using deep learning based on genomic and clinical data and preliminarily applied in clinic. Genetic characterization of CUP patients contributes to the selection of targeted therapies under unclear diagnosis, whereas our diagnosis model could equally adjust more proper precision treatment for CUP patients. In CUP patients, the combined strategy of deep learning-predicted diagnosis and genetic mutations-based therapy could help to maximize the clinical benefit in a clinical setting and optimize the clinical development of innovative therapies.
Study EV-104: Phase 1 study of intravesical enfortumab vedotin for treatment of patients with Non-Muscle Invasive Bladder Cancer (NMIBC) (Trial in Progress)
Authors: A.M. Kamat, G. Steinberg, B. Inman, M. Kates, E. Uchio, S. Porten, M. Rouperet, J. Palou, J. Catto, G.S. Kulkarni, T. Powles, M. Tyson, G. Haas, X. Ding, S. Narayanan, Y. Lotan
Journal: European Urology (2022)
Concrete resource needs and frailty among older adults with cancer: The Cancer and Aging Resilience Evaluation (CARE) Registry.
Authors: Grant Richard Williams, Smith Giri, Chen Dai, Mustafa Al-Obaidi, Christian Harmon, Kira Bona, Wendy Landier, Smita Bhatia, Julie Anna Wolfson
Journal: Journal of Clinical Oncology (2022)

6546 Background: Concrete resource needs (CRN: insecurity of food, utilities, and/or housing) are important and modifiable indicators of poverty. Prior work among adults with chronic cardiometabolic diseases demonstrates that CRN-targeted interventions improve health outcomes. Poverty is associated with inferior health outcomes among patients with cancer. Frailty is a recognized state of increased vulnerability and is associated with increased toxicities from cancer therapies and reduced survival. The prevalence of CRN among older adults with cancer and its role in modifying the risk of frailty remains unknown. We aimed to (1) describe the prevalence of CRN and (2) examine the association between CRN and frailty among older adults with cancer. Methods: The CARE registry prospectively enrolls older adults (≥60y) with cancer seen at UAB as new patients. Single-item screening measures captured food, housing and utility insecurity in addition to the baseline CARE geriatric assessment beginning 8/2020. The 44-item CARE Frailty Index (based on the principles of deficit accumulation) was used to define frailty. Multivariable analysis examined association of CRN with frailty, adjusting for age, race, sex, education, employment, marital status, and cancer type and stage. Results: The cohort included 485 participants with a mean age at enrollment of 69y; 63.7% were male; 20.4% were non-Hispanic Black. The most prevalent cancer types included colorectal (33.0%), pancreatic (16.3%) and hepatobiliary (12.2%) cancers. Median time from cancer diagnosis to study enrollment was 35 days. The overall prevalence of CRN was 6.6% (insecurity of housing [2.9%], food [4.3%], and utilities [4.1%]). Participants with CRN were less educated ( &lt; HS: 21.9% vs. 9.9%, p= 0.01), more often widowed/divorced (53.1% vs. 35.1%, p= 0.003) and more likely to be disabled (43.8% vs. 12.4%, p&lt; 0.001). Overall, 33.8% of patients were frail. In multivariable analysis, patients with CRN had a 6.24 higher odds of frailty (95% CI 1.72-22.7, p= 0.005) compared to those without CRN after adjustment for above-mentioned covariates. Conclusions: CRN represents a novel exposure that is independently associated with frailty. In order to inform a CRN-targeted intervention for the growing number of older adults with cancer, future work is warranted to examine the CRN construct in this population, including examination of more detailed screening measures and CRN-associated cancer outcomes.